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16 results on '"MESH: Receptors, Glucocorticoid"'

1. The Nuclear Receptor Superfamily: A Personal Retrospect on the First Two Decades

Author

Pierre Chambon, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I

Subjects
MESH: Signal Transduction, Time Factors, Transcription, Genetic, Receptors, Retinoic Acid, MESH: Receptors, Glucocorticoid, Receptors, Cytoplasmic and Nuclear, Mice, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, MESH: Animals, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, MESH: DNA, SUPERFAMILY, General Medicine, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), MESH: Retinoid X Receptors, MESH: History, 20th Century, Signal transduction, Dimerization, Signal Transduction, MESH: Body Patterning, MESH: Cell Line, Tumor, MESH: Mutation, MESH: Receptors, Cytoplasmic and Nuclear, Biology, 03 medical and health sciences, Receptors, Glucocorticoid, Cell Line, Tumor, Animals, Humans, MESH: Endocrinology, MESH: Mice, Molecular Biology, Body Patterning, 030304 developmental biology, MESH: Receptors, Retinoic Acid, MESH: Humans, MESH: Transcription, Genetic, MESH: Time Factors, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, History, 20th Century, Retinoid X Receptors, MESH: Dimerization, Nuclear receptor, chemistry, Mutation
Abstract

International audience

Published
2005

2. The MAPK pathway and Egr-1 mediate stress-related behavioral effects of glucocorticoids

Author

Pier Vincenzo Piazza, Jean-Michel Revest, Aline Desmedt, Françoise Rougé-Pont, Francesco Di Blasi, Pierre Kitchener, François Tronche, Marc Turiault, Génétique moléculaire, neurophysiologie et comportement (GMNC), Centre National de la Recherche Scientifique (CNRS), Aquitaine, Physiopathologie de la plasticité neuronale, Université Bordeaux Segalen - Bordeaux 2, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MAPK/ERK pathway, MESH: Hippocampus, MESH: Receptors, Glucocorticoid, [SDV]Life Sciences [q-bio], MESH: Cricetinae, MESH: Fear, Hippocampus, Endogeny, Mice, 0302 clinical medicine, Glucocorticoid receptor, Cricetinae, Chlorocebus aethiops, MESH: Up-Regulation, MESH: Early Growth Response Protein 1, MESH: Animals, MESH: Memory, Enzyme Inhibitors, MESH: Stress, Physiological, Receptor, 0303 health sciences, Chemistry, General Neuroscience, Neurodegeneration, Fear, MESH: Transcription Factors, Up-Regulation, 3. Good health, DNA-Binding Proteins, MESH: COS Cells, medicine.anatomical_structure, MESH: Enzyme Inhibitors, COS Cells, hormones, hormone substitutes, and hormone antagonists, Astrocyte, medicine.medical_specialty, MAP Kinase Signaling System, CHO Cells, Immediate-Early Proteins, 03 medical and health sciences, Receptors, Glucocorticoid, Memory, Stress, Physiological, MESH: CHO Cells, MESH: Mice, Inbred C57BL, Internal medicine, medicine, Animals, RNA, Messenger, Glucocorticoids, MESH: Mice, Early Growth Response Protein 1, MESH: RNA, Messenger, 030304 developmental biology, MESH: MAP Kinase Signaling System, MESH: Immediate-Early Proteins, medicine.disease, MESH: Cercopithecus aethiops, Mice, Inbred C57BL, Endocrinology, Nuclear receptor, MESH: Glucocorticoids, Neuroscience, MESH: DNA-Binding Proteins, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; Many of the behavioral consequences of stress are mediated by the activation of the glucocorticoid receptor by stress-induced high levels of glucocorticoid hormones. To explore the molecular mechanisms of these effects, we combined in vivo and in vitro approaches. We analyzed mice carrying a brain-specific mutation (GR(NesCre)) in the glucocorticoid receptor gene (GR, also called Nr3c1) and cell lines that either express endogenous glucocorticoid receptor or carry a constitutively active form of the receptor (DeltaGR) that can be transiently induced. In the hippocampus of the wild-type [corrected] mice after stress, as well as in the cell lines, activation of glucocorticoid receptors greatly increased the expression and enzymatic activity of proteins in the MAPK signaling pathway and led to an increase in the levels of both Egr-1 mRNA and protein. In parallel, inhibition of the MAPK pathway within the hippocampus abolished the increase in contextual fear conditioning induced by glucocorticoids. The present results provide a molecular mechanism for the stress-related effects of glucocorticoids on fear memories.

Published
2005

3. BDNF-TrkB signaling through Erk1/2MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids

Author

P.V. Piazza, Françoise Rougé-Pont, A. Y. Le Roux, N Kaouane, J-M Revest, Aline Desmedt, Monique Vallée, Valérie Roullot-Lacarrière, F Tronche, Fernando Kasanetz, Mines Nantes (Mines Nantes), UMR 5228, Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique moléculaire, neurophysiologie et comportement, Expression des Gènes et comportement adaptatifs = Molecular Genetics, Neurophysiology and Behavior (NPS-15), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, Agence Nationale pour la Recherche (ANR), Federation Bordeaux Neurosciences (FBN), University Victor Segalen-Bordeaux2, Conseil Regional d'Aquitaine, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, and Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS)

Subjects
Male, MESH: Hippocampus, MESH: Receptors, Glucocorticoid, [SDV]Life Sciences [q-bio], MESH: Fear, Hippocampus, MESH: Rats, Sprague-Dawley, Tropomyosin receptor kinase B, MESH: Brain-Derived Neurotrophic Factor, Rats, Sprague-Dawley, Tissue Culture Techniques, 0302 clinical medicine, Glucocorticoid receptor, MESH: Tissue Plasminogen Activator, MESH: Animals, MESH: Memory, Phosphorylation, Receptor, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, tissue plasminogen activator, contextual fear memory, glucocorticoids, MESH: Receptor, trkB, brain-derived neurotrophic factor, MESH: Stress, Psychological, Fear, Psychiatry and Mental health, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal transduction, Psychology, MESH: Mice, Transgenic, MAP Kinase Signaling System, Transgene, Mice, Transgenic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Receptors, Glucocorticoid, MESH: Mice, Inbred C57BL, Memory, Animals, Receptor, trkB, MESH: Tissue Culture Techniques, tropomyosin-related kinase B, Molecular Biology, extracellular signal-regulated kinases 1/2 mitogen-activated protein kinase, 030304 developmental biology, Brain-derived neurotrophic factor, MESH: Phosphorylation, MESH: MAP Kinase Signaling System, [SCCO.NEUR]Cognitive science/Neuroscience, MESH: Male, Mice, Inbred C57BL, Neuroscience, Stress, Psychological, 030217 neurology & neurosurgery
Abstract

International audience; Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2(MAPK) signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.

Published
2014

4. Peroxisome proliferator-activated receptor-γ activation induces 11β-hydroxysteroid dehydrogenase type 1 activity in human alternative macrophages

Author

Christian Duhem, Corinne Copin, Bernardette Neve, Bruno Derudas, Jérôme Eeckhoute, Bernard Noël, Mohamed Amine Bouhlel, Bart Staels, Jonathan R. Seckl, Giulia Chinetti-Gbaguidi, Philippe Lefebvre, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Endocrinology Unit, University of Edinburgh-Queen's Medical Researche Institute, University of Edinburgh, This work was supported by grants from the Nouvelle Société Française d'Athérosclérose/Sanofi-Aventis (to M.A.Bouhlel), the Région Nord-Pas de Calais/FEDER (ChoMetAlt project), the Fondation Coeur et Artères and theAgence Nationale de la Recherche (AlMHA project). G. Chinetti-Gbaguidi is a recipient of aContrat d'Interface from the CHRU de Lille., Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Derudas, Marie-Hélène

Subjects
MESH: Inflammation, Time Factors, PPARgamma, Hydrocortisone, MESH: Receptors, Glucocorticoid, Peroxisome proliferator-activated receptor, MESH: Thiazolidinediones, 0302 clinical medicine, Glucocorticoid receptor, 11β-hydroxysteroid dehydrogenase type 1, Genes, Reporter, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Receptor, Cells, Cultured, chemistry.chemical_classification, 0303 health sciences, biology, MESH: Hydrocortisone, Cell biology, GR, Enzyme Induction, human alternative macrophages, MESH: 11-beta-Hydroxysteroid Dehydrogenase Type 1, RNA Interference, Cardiology and Cardiovascular Medicine, Glucocorticoid, hormones, hormone substitutes, and hormone antagonists, medicine.drug, MESH: Cells, Cultured, medicine.medical_specialty, MESH: Enzyme Induction, MESH: RNA Interference, Macrophage polarization, Transfection, 11beta-HSDI, Article, Proinflammatory cytokine, Rosiglitazone, 03 medical and health sciences, Receptors, Glucocorticoid, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Humans, Macrophages, MESH: Transfection, MESH: Time Factors, MESH: Genes, Reporter, MESH: Macrophages, MESH: Interleukin-4, Cortisone, PPAR gamma, Endocrinology, Nuclear receptor, chemistry, MESH: PPAR gamma, inflammation, biology.protein, Thiazolidinediones, Interleukin-4, MESH: Cortisone, 030217 neurology & neurosurgery
Abstract

Objective— 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the intracellular reduction of inactive cortisone to active cortisol, the natural ligand activating the glucocorticoid receptor (GR). Peroxisome proliferator– activated receptor-γ (PPARγ) is a nuclear receptor controlling inflammation, lipid metabolism, and the macrophage polarization state. In this study, we investigated the impact of macrophage polarization on the expression and activity of 11β-HSD1 and the role of PPARγ therein. Methods and Results— 11β-HSD1 gene expression is higher in proinflammatory M1 and anti-inflammatory M2 macrophages than in resting macrophages, whereas its activity is highest in M2 macrophages. Interestingly, PPARγ activation induces 11β-HSD1 enzyme activity in M2 macrophages but not in resting macrophages or M1 macrophages. Consequently, human M2 macrophages displayed enhanced responsiveness to the 11β-HSD1 substrate cortisone, an effect amplified by PPARγ induction of 11β-HSD1 activity, as illustrated by an increased expression of GR target genes. Conclusion— Our data identify a positive cross-talk between PPARγ and GR in human M2 macrophages via the induction of 11β-HSD1 expression and activity.

Published
2012

5. The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib

Author

A. Y. Le Roux, Jacques Barik, Aline Desmedt, J-M Revest, N Kaouane, Françoise Rougé-Pont, Monique Vallée, M Mondin, François Tronche, P.V. Piazza, UMR 5228, Centre National de la Recherche Scientifique (CNRS), Mines Nantes (Mines Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique moléculaire, neurophysiologie et comportement, and Aquitaine

Subjects
MAPK/ERK pathway, Male, Egr-1, MESH: Signal Transduction, MESH: Hippocampus, MESH: Receptors, Glucocorticoid, [SDV]Life Sciences [q-bio], MESH: Neurons, MESH: Rats, Sprague-Dawley, Hippocampus, PC12 Cells, Second Messenger Systems, MESH: Mice, Knockout, MESH: Association Learning, MESH: Synapsins, Rats, Sprague-Dawley, Mice, 0302 clinical medicine, Glucocorticoid receptor, MESH: Early Growth Response Protein 1, MESH: Animals, MESH: Memory, Receptor, MESH: Avoidance Learning, ComputingMilieux_MISCELLANEOUS, MESH: Mice, Neurologic Mutants, Mice, Knockout, Neurons, 0303 health sciences, MESH: Statistics, Nonparametric, glucocorticoids, MESH: Stress, Psychological, Cell biology, glucocorticoids (GC), Glucocorticoid Receptors (GR), Psychiatry and Mental health, Second messenger system, Phosphorylation, Original Article, Signal transduction, Mitogen-Activated Protein Kinases, stress-related memory, Glucocorticoid, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Signal Transduction, medicine.medical_specialty, MESH: Rats, MESH: Mice, Transgenic, Mice, Transgenic, Biology, Statistics, Nonparametric, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, Neurologic Mutants, Receptors, Glucocorticoid, Memory, MESH: Mice, Inbred C57BL, Internal medicine, MESH: Analysis of Variance, medicine, Avoidance Learning, Animals, MESH: PC12 Cells, Molecular Biology, Transcription factor, MESH: Mice, 030304 developmental biology, Early Growth Response Protein 1, Analysis of Variance, [SCCO.NEUR]Cognitive science/Neuroscience, Association Learning, glucocorticoid receptors, Synapsins, MAPK, MESH: Mitogen-Activated Protein Kinases, MESH: Male, Rats, synapsin-Ia/Ib, MESH: Second Messenger Systems, Mice, Inbred C57BL, Endocrinology, nervous system, MESH: Corticosterone, Corticosterone, 030217 neurology & neurosurgery, Stress, Psychological
Abstract

International audience; The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GR(NesCre)), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress.

Published
2010

6. Medical treatment of Cushing's syndrome: glucocorticoid receptor antagonists and mifepristone

Author

Frederic Castinetti, Bernard Conte-Devolx, Thierry Brue, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, MESH: Receptors, Glucocorticoid, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Adrenocorticotropic hormone, MESH: Cushing Syndrome, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Cushing syndrome, 0302 clinical medicine, Endocrinology, Glucocorticoid receptor, Hormone Antagonists, Receptors, Glucocorticoid, Internal medicine, Medicine, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cushing Syndrome, MESH: Humans, Endocrine and Autonomic Systems, business.industry, Antiglucocorticoid, Mifepristone, Cushing's disease, medicine.disease, Hypokalemia, 3. Good health, Blood pressure, chemistry, MESH: Mifepristone, 030220 oncology & carcinogenesis, MESH: Hormone Antagonists, medicine.symptom, business, medicine.drug
Abstract

International audience; Mifepristone is the first and only available glucocorticoid receptor antagonist. It was initially mainly considered as a so-called 'contragestive' pill due to its antiprogestin activity. In this review, we summarize the results of mifepristone reported in the literature as a treatment of Cushing's syndrome. Most of the patients were treated due to unsuccessful surgery and/or partially effective anticortisolic drugs. The majority of them presented a rapid decrease of clinical signs of hypercortisolism during the first month of treatment; about half experienced a reduction in their elevated blood pressure, and half of the diabetic patients presented improved blood glucose levels. Mifepristone treatment has 2 main drawbacks: (1) the blockade of glucocorticoid receptors leads to increased ACTH and cortisol levels, making it difficult to adapt the treatment and diagnose adrenal deficiency, and (2) increased cortisol levels can also lead to severe hypokalemia. Follow-up of efficacy should only be clinical (weight, blood pressure, skin lesions) and biological (regular blood potassium sampling). Dose adjustment will be performed based on these parameters. The lack of a large available prospective cohort of patients on mifepristone, and the scarcity of data on its long-term effects, does not allow recommending it as a first-line drug in the treatment of hypercortisolism. However, as mifepristone is a rapidly effective drug, it can play a role in the management of hypercortisolism. The main indication is the partial efficacy or bad tolerance of other well-known anticortisolic drugs, either by replacement (bad tolerance, lack of effectiveness) or addition (multimodal approach) of mifepristone.

Published
2010

7. Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates

Author

Martinerie, Laetitia, Viengchareun, Say, Delezoïde, Anne-Lise, Jaubert, Francis, Sinico, Martine, Prevot, Sophie, Boileau, Pascal, Meduri, Géri, Lombès, Marc, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biologie du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'AnatomoPathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Créteil, Service d'Anatomie et de Cytologie Pathologiques [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Antoine-Béclère, Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'endocrinologie, Service d'Endocrinologie et Maladies de la reproduction, This work was supported by funds from Inserm, University Paris-Sud 11 (BQR) and the European Section of Aldosterone Council (ESAC). Fellowships (to LM) were from the Association des Juniors en Pédiatrie, the Société Française d'Endocrinologie et Diabétologie Pédiatrique, Gallia and Pfizer Laboratories, France, and the Fonds d'Etudes et de Recherche du Corps Médical des hôpitaux de Paris., and Lombes, Marc

Subjects
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, aldosterone, MESH: Aquaporin 2, MESH: Humans, MESH: Renin, renal development, MESH: Receptors, Glucocorticoid, MESH: Infant, Newborn, MESH: Aldosterone, MESH: Epithelial Sodium Channel, MESH: Kidney, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Male, MESH: Renin-Angiotensin System, MESH: Receptors, Mineralocorticoid, MESH: 11-beta-Hydroxysteroid Dehydrogenase Type 2, MESH: Drug Resistance, MESH: Animals, MESH: Receptors, Vasopressin, MESH: Mice, MESH: Female, mineralocorticoid receptor
Abstract

International audience; The human neonatal period is characterized by renal immaturity with impaired capacity to regulate water and sodium homeostasis, resembling partial aldosterone resistance. Because aldosterone effects are mediated by the mineralocorticoid receptor (MR), we postulated that this hormonal unresponsiveness could be related to low MR expression in the distal nephron. We measured aldosterone and renin levels in umbilical cord blood of healthy newborns. We used quantitative real-time PCR and immunohistochemistry to analyze the expression of MR and key players of the mineralocorticoid signaling pathway during human and mouse renal development. High aldosterone and renin levels were found at birth. MR mRNA was detected in mouse kidney at d 16 postcoitum, peaking at d 18 postcoitum, but its expression was surprisingly very low at birth, rising progressively afterward. Similar biphasic temporal expression was observed during human renal embryogenesis, with a transient expression between 15 and 24 wk of gestation but an undetectable immunoreactive MR in late gestational and neonatal kidneys. This cyclic MR expression was tightly correlated with the evolution of the 11beta-hydroxysteroid dehydrogenase type 2 and the epithelial sodium channel alpha-subunit. In contrast, glucocorticoid and vasopressin receptors and aquaporin 2 followed a progressive and sustained evolution during renal maturation. Our study provides the first evidence for a low renal MR expression level at birth, despite high aldosterone levels, which could account for compromised postnatal sodium handling. Elucidation of regulatory mechanisms governing MR expression should lead to new strategies for the management of sodium waste in preterms and neonates.

Published
2009

8. Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates.: MR and renal maturation

Author

Sophie Prevot, Anne-Lise Delezoide, Say Viengchareun, Marc Lombès, Francis Jaubert, Laetitia Martinerie, Pascal Boileau, Martine Sinico, Geri Meduri, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Service de Biologie du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'AnatomoPathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Créteil, Service d'Anatomie et de Cytologie Pathologiques [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Antoine-Béclère, Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'endocrinologie, Service d'Endocrinologie et Maladies de la reproduction, This work was supported by funds from Inserm, University Paris-Sud 11 (BQR) and the European Section of Aldosterone Council (ESAC). Fellowships (to LM) were from the Association des Juniors en Pédiatrie, the Société Française d'Endocrinologie et Diabétologie Pédiatrique, Gallia and Pfizer Laboratories, France, and the Fonds d'Etudes et de Recherche du Corps Médical des hôpitaux de Paris., Université Paris-Sud - Paris 11 (UP11) - IFR93 - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Robert Debré - Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Antoine-Béclère, Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, and Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre

Subjects
Male, Epithelial sodium channel, Receptors, Vasopressin, MESH: Renin, MESH: Receptors, Glucocorticoid, Drug Resistance, Kidney, Renin-Angiotensin System, Mice, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Mineralocorticoid receptor, MESH: Renin-Angiotensin System, 11-beta-Hydroxysteroid Dehydrogenase Type 2, MESH: Receptors, Mineralocorticoid, Renin, MESH: Animals, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Aldosterone, MESH: Infant, Newborn, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.anatomical_structure, Aquaporin 2, MESH: 11-beta-Hydroxysteroid Dehydrogenase Type 2, MESH: Drug Resistance, Female, MESH: Receptors, Vasopressin, medicine.medical_specialty, medicine.drug_class, 030209 endocrinology & metabolism, MESH: Epithelial Sodium Channel, Biology, Article, 03 medical and health sciences, Receptors, Glucocorticoid, Internal medicine, Renin–angiotensin system, medicine, Animals, Humans, Epithelial Sodium Channels, MESH: Mice, 030304 developmental biology, mineralocorticoid receptor, aldosterone, MESH: Aquaporin 2, MESH: Humans, renal development, Infant, Newborn, MESH: Aldosterone, MESH: Kidney, MESH: Male, Receptors, Mineralocorticoid, chemistry, Mineralocorticoid, MESH: Female, Homeostasis
Abstract

International audience; The human neonatal period is characterized by renal immaturity with impaired capacity to regulate water and sodium homeostasis, resembling partial aldosterone resistance. Because aldosterone effects are mediated by the mineralocorticoid receptor (MR), we postulated that this hormonal unresponsiveness could be related to low MR expression in the distal nephron. We measured aldosterone and renin levels in umbilical cord blood of healthy newborns. We used quantitative real-time PCR and immunohistochemistry to analyze the expression of MR and key players of the mineralocorticoid signaling pathway during human and mouse renal development. High aldosterone and renin levels were found at birth. MR mRNA was detected in mouse kidney at d 16 postcoitum, peaking at d 18 postcoitum, but its expression was surprisingly very low at birth, rising progressively afterward. Similar biphasic temporal expression was observed during human renal embryogenesis, with a transient expression between 15 and 24 wk of gestation but an undetectable immunoreactive MR in late gestational and neonatal kidneys. This cyclic MR expression was tightly correlated with the evolution of the 11beta-hydroxysteroid dehydrogenase type 2 and the epithelial sodium channel alpha-subunit. In contrast, glucocorticoid and vasopressin receptors and aquaporin 2 followed a progressive and sustained evolution during renal maturation. Our study provides the first evidence for a low renal MR expression level at birth, despite high aldosterone levels, which could account for compromised postnatal sodium handling. Elucidation of regulatory mechanisms governing MR expression should lead to new strategies for the management of sodium waste in preterms and neonates.

Published
2009

9. Interference of progestins with endothelial actions of estrogens: a matter of glucocorticoid action or deprivation?

Author

Pierre Gourdy, Tommaso Simoncini, Jean-François Arnal, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Reproductive Medicine and Child Development, University of Pisa - Università di Pisa, Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Pise

Subjects
MESH: Receptors, Progesterone, medicine.medical_specialty, medicine.drug_class, MESH: Receptors, Glucocorticoid, medicine.medical_treatment, Placebo, Internal medicine, MESH: Progesterone, medicine, Medroxyprogesterone acetate, MESH: Animals, MESH: Endothelial Cells, MESH: Thrombosis, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ComputingMilieux_MISCELLANEOUS, MESH: Platelet Aggregation, MESH: Humans, business.industry, Hazard ratio, medicine.disease, MESH: Estrogen Replacement Therapy, Menopause, Endocrinology, MESH: Randomized Controlled Trials as Topic, Estrogen, MESH: Nitric Oxide, MESH: Progesterone Congeners, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Hormone therapy, MESH: Coronary Disease, MESH: Estradiol, Cardiology and Cardiovascular Medicine, business, MESH: Glucocorticoids, Progestin, MESH: Women's Health, MESH: Female, MESH: Nitric Oxide Synthase Type III, medicine.drug, Cohort study, MESH: Cells, Cultured
Abstract

Estrogens play a pivotal role in sexual development and reproduction and are also implicated in a number of physiological processes in various tissues including the cardiovascular system. Epidemiological evidence suggests that endogenous estrogens protect women against coronary heart disease (CHD) before the age of menopause, and decreased CHD risk among postmenopausal women has been for a long time the main expected benefit of hormone therapy (HT).1 However, from the publication of the Women Health Initiative (WHI) results,2 medical practices of HT have been dramatically altered. Unexpectedly, large randomized controlled trials failed to demonstrate a beneficial effect of HT (conjugated equine estrogens combined [CEE] with medroxyprogesterone acetate [MPA]) for both secondary (Heart and Estrogen/Progestin Replacement Study [HERS])3 and primary CHD prevention (Women’s Health Initiative study [WHI]),2 and even revealed a detrimental effect during the year after the initiation of the HT. When women enrolled in the WHI study were divided according to the delay between onset of menopause and initiation of HT, the coronary risk tended to be lowered compared to placebo when HT is initiated during the first 10 years after menopause (hazard ratio for CHD=0.88).4 However, this risk tended to increase when HT was started 10 to 19 years postmenopause (hazard ratio for CHD=1.23), and the increase was significant when HT was started after more than 20 years (hazard ratio for CHD=1.66). See accompanying article on page 586 In striking contrast, and in line with epidemiological and cohort studies suggesting a protective effect of estradiol (E2), a large amount of data from experimental models of atherosclerosis (from mouse to monkey) demonstrated that endogenous as well as exogenous E2 …

Published
2009

10. Corticosterone alters AMPAR mobility and facilitates bidirectional synaptic plasticity

Author

Jeremy M. Henley, David Holman, Harmen J. Krugers, Olof Wiegert, Marian Joëls, Myrrhe van Spronsen, Ming Zhou, Casper C. Hoogenraad, Stéphane Martin, Structural and Functional Plasticity of the nervous system (SILS, FNWI), MRC Centre for Synaptic Plasticity, University of Bristol [Bristol], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), SILS-CNS, University of Amsterdam [Amsterdam] (UvA), Department of Neuroscience, Erasmus University Medical Center [Rotterdam] (Erasmus MC), and Neurosciences

Subjects
MESH: Hippocampus, MESH: Receptors, Glucocorticoid, Anti-Inflammatory Agents, MESH: Neurons, Nonsynaptic plasticity, lcsh:Medicine, Hippocampus, Synaptic Transmission, chemistry.chemical_compound, 0302 clinical medicine, Corticosterone, MESH: Animals, MESH: Neuronal Plasticity, lcsh:Science, Neurons, 0303 health sciences, Neuronal Plasticity, Neuroscience/Behavioral Neuroscience, MESH: Electrophysiology, Multidisciplinary, Synaptic scaling, Neuroscience/Animal Cognition, Endocytosis, Electrophysiology, MESH: N-Methylaspartate, MESH: Adaptor Protein Complex 2, MESH: Receptors, AMPA, MESH: Endocytosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Fluorescence Recovery After Photobleaching, Research Article, medicine.medical_specialty, N-Methylaspartate, MESH: Rats, Adaptor Protein Complex 2, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, AMPA receptor, Biology, 03 medical and health sciences, Receptors, Glucocorticoid, Internal medicine, Synaptic augmentation, Metaplasticity, Neuroscience/Neuronal Signaling Mechanisms, MESH: Synaptic Transmission, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Receptors, AMPA, 030304 developmental biology, lcsh:R, Rats, Endocrinology, Synaptic fatigue, chemistry, nervous system, MESH: Anti-Inflammatory Agents, Synaptic plasticity, lcsh:Q, MESH: Corticosterone, Neuroscience, MESH: Fluorescence Recovery After Photobleaching, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND: The stress hormone corticosterone has the ability both to enhance and suppress synaptic plasticity and learning and memory processes. However, until today there is very little known about the molecular mechanism that underlies the bidirectional effects of stress and corticosteroid hormones on synaptic efficacy and learning and memory processes. In this study we investigate the relationship between corticosterone and AMPA receptors which play a critical role in activity-dependent plasticity and hippocampal-dependent learning. METHODOLOGY/PRINCIPAL FINDINGS: Using immunocytochemistry and live cell imaging techniques we show that corticosterone selectively increases surface expression of the AMPAR subunit GluR2 in primary hippocampal cultures via a glucocorticoid receptor and protein synthesis dependent mechanism. In agreement, we report that corticosterone also dramatically increases the fraction of surface expressed GluR2 that undergo lateral diffusion. Furthermore, our data indicate that corticosterone facilitates NMDAR-invoked endocytosis of both synaptic and extra-synaptic GluR2 under conditions that weaken synaptic transmission. CONCLUSION/SIGNIFICANCE: Our results reveal that corticosterone increases mobile GluR2 containing AMPARs. The enhanced lateral diffusion properties can both facilitate the recruitment of AMPARs but under appropriate conditions facilitate the loss of synaptic AMPARs (LTD). These actions may underlie both the facilitating and suppressive effects of corticosteroid hormones on synaptic plasticity and learning and memory and suggest that these hormones accentuate synaptic efficacy.

Published
2009

11. Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women

Author

Claus Holst, Nathalie Vega, Moira A. Taylor, J. Alfredo Martínez, Eva Klimcakova, Thorkild I. A. Sørensen, Dominique Langin, Sébastien Déjean, Jean M. Oppert, Peter Arner, Hubert Vidal, Nathalie Viguerie, Karine Clément, Frédéric Capel, Wim H. M. Saris, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche sur les obésités, CHU Toulouse [Toulouse]-Laboratoire, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Lyon-Sud, FACULTE DE LYON, Centre de Recherche en Nutrition Humaine, Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Midicine Karolinska Institute, Karolinska University Hospital Huddinge, Department of Sports Medicine of Charles University, Faculty of Medicine Charles University, Department of Physiology and nutrition University of Navarra, Universidad de Navarra [Pamplona] (UNAV), Department of Human Biology Nutrition and Toxicology Research Institute, Maastricht University [Maastricht], The Netherlands Institute of Preventive Medicine, Institute of Preventive Medicine, School of Biomedical Sciences Queen's Medical Center, University of Nottingham Medical School, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse, Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Nutrition and Endocrinology AP / HP, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR 31 Louis Bugnard ( IFR 31 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Institut de Mathématiques de Toulouse UMR5219 ( IMT ), Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Navarra [Pamplona] ( UNAV ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Humane Biologie, RS: NUTRIM - R1 - Metabolic Syndrome, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Transcription, Genetic, Endocrinology, Diabetes and Metabolism, MESH: Energy Intake, Biochemistry, Body Mass Index, 0302 clinical medicine, Endocrinology, Gene expression, MESH: Genetic Variation, MESH : Adaptor Proteins, Signal Transducing, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Addipose tissue, Reducing, MESH: Mitochondrial Proteins, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, Body Composition, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, MESH : Body Composition, MESH : Adipose Tissue, MESH: Body Mass Index, MESH : Receptors, Glucocorticoid, 03 medical and health sciences, MESH: Weight Loss, Genetic, Humans, MESH : Fatty Acid-Binding Proteins, MESH : Mitochondrial Proteins, MESH: Adaptor Proteins, Signal Transducing, MESH: Humans, MESH : Humans, Signal Transducing, Genetic Variation, MESH: Adult, Autophagy-Related Protein 8 Family, MESH: Body Composition, medicine.disease, Obesity, MESH : Energy Metabolism, MESH : Body Mass Index, Energy intake, Body mass index, MESH: Female, Candidate gene, MESH: Receptors, Glucocorticoid, Clinical Biochemistry, Adipose tissue, Blood lipids, Glucocorticoid, Weight loss, Sirtuin 3, Receptors, MESH : RNA, Sirtuins, MESH: Obesity, MESH : Female, Nutrición y dietética [Ciencias de la Salud], MESH : Diet, Reducing, 2. Zero hunger, MESH : Sirtuins, MESH: Diet, Reducing, Microfilament Proteins, MESH: Energy Metabolism, Adaptor Proteins, MESH : Adult, MESH: Sirtuins, MESH : Obesity, Female, medicine.symptom, Transcription, Adult, MESH : Microfilament Proteins, 030209 endocrinology & metabolism, Context (language use), Biology, Fatty Acid-Binding Proteins, MESH: Fatty Acid-Binding Proteins, Mitochondrial Proteins, MESH: Microfilament Proteins, Receptors, Glucocorticoid, MESH : Genetic Variation, MESH: RNA, Internal medicine, Weight Loss, medicine, 030304 developmental biology, Adaptor Proteins, Signal Transducing, MESH: Transcription, Genetic, Biochemistry (medical), MESH : Transcription, Genetic, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, RNA, MESH : Weight Loss, Energy Intake, Energy Metabolism
Abstract

Context: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. Objective: We investigated adipose tissue gene expression from human obese women according to energy deficit and, the fat and carbohydrate content of the diet. Design & setting: Obese subjects recruited among 8 European clinical centers followed 10 weeks of either a low fat (high carbohydrate) or a moderate fat (low carbohydrate) hypoenergetic diet. Subjects: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. Main Outcome Measure: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. Results: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. A thousand genes were regulated by energy restriction. We validated an effect of the fat-to-carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA and GABARAPL2) with increased expression during the moderate fat diet. Conclusions: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response. AD - INSERM, U858, Laboratoire de Recherches sur les Obesites, Institut de Medecine Moleculaire de Rangueil, Toulouse; Universite Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse; Centre Hospitalier Universitaire de Toulouse, France; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; INSERM, UMR -870; INRA U-1235; Faculte de Medecine Lyon-Sud universite de Lyon 1; Centre de Recherche en Nutrition Humaine, Hospices civils de Lyon; Lyon, France; Institut de Mathematiques de Toulouse UMR 5219, Universite Paul-Sabatier, Toulouse, France; Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Sports Medicine, Centre of Preventive Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain; Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands; Institute of Preventive Medicine, Centre for Health and Society, Copenhagen University Hospital, Copenhagen, Denmark; School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham Medical School, Nottingham, United Kingdom; INSERM, Nutriomique U872 (Team 7), 75004 Paris, France; Universites Pierre et Marie Curie-Paris6, UMR-S 872, Cordelier Research Center & Paris Descartes, 75006 Paris; and Assistance Publique/Hopitaux de Paris (AP-HP), Pitie Salpetriere Hospital, Nutrition and Endocrinology department, 75013 Paris, France.

Published
2008

12. Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats

Author

Joerg Rossbacher, Pascale Perret, Katsutaro Morino, Esben S. Buhl, Dongyan Zhang, Varman T. Samuel, Allan Flyvbjerg, Susanne Neschen, Jung H. Kim, Kitt Falk Petersen, Gary W. Cline, Shin Yonemitsu, Department of Pharmacology, Medical Research Laboratory, Department of Internal Medicine, Yale University School of Medicine, Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Yale School of Medicine [New Haven, Connecticut] (YSM), and Perret, Pascale

Subjects
Physiology, MESH: Receptors, Glucocorticoid, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MESH: Random Allocation, MESH: Insulin-Like Growth Factor I, Pituitary-Adrenal System, Type 2 diabetes, MESH: Rats, Sprague-Dawley, MESH: Animals, Newborn, Rats, Sprague-Dawley, Random Allocation, chemistry.chemical_compound, Hypothalamic-Pituitary-Adrenal Axis, 0302 clinical medicine, MESH: Pregnancy, MESH: Cholesterol, Pregnancy, Corticosterone, MESH: Reverse Transcriptase Polymerase Chain Reaction, Insulin, MESH: Animals, Insulin-Like Growth Factor I, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH: Insulin-Like Growth Factor Binding Protein 1, Fasting, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Restraint, Physical, MESH: Glucose, MESH: Insulin Resistance, Cholesterol, medicine.anatomical_structure, Liver, MESH: Pituitary-Adrenal System, Female, Hypothalamic–pituitary–adrenal axis, Restraint, Physical, MESH: Triglycerides, Hypothalamo-Hypophyseal System, medicine.medical_specialty, MESH: Rats, MESH: Fasting, 030209 endocrinology & metabolism, Adrenocorticotropic hormone, MESH: Insulin, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Biology, MESH: Hypothalamo-Hypophyseal System, Article, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Receptors, Glucocorticoid, Insulin resistance, Adrenocorticotropic Hormone, Downregulation and upregulation, Physiology (medical), Internal medicine, medicine, Animals, MESH: Adrenocorticotropic Hormone, Triglycerides, 030304 developmental biology, Low Birth Weight, MESH: Phosphoenolpyruvate Carboxykinase (ATP), medicine.disease, Rats, Insulin-Like Growth Factor Binding Protein 1, Glucose, Endocrinology, Hepatic Insulin Resistance, Animals, Newborn, chemistry, Prenatal stress, Insulin Resistance, MESH: Corticosterone, MESH: Female, Phosphoenolpyruvate Carboxykinase (ATP), MESH: Liver
Abstract

International audience; Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an approximately 70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance.

Published
2007

13. Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice

Author

Martine Gehin, Dieter Fischer, Siegmund Wolf, Alexandre V. Patchev, Miles Herkenham, Osborne F. X. Almeida, Vladimir K. Patchev, Pierre Chambon, Franziska Götz, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I

Subjects
Male, MESH: Receptors, Glucocorticoid, medicine.medical_treatment, Pituitary-Adrenal System, MESH: Base Sequence, Steroidogenic Factor 1, MESH: Mice, Knockout, Biochemistry, chemistry.chemical_compound, Mice, Nuclear Receptor Coactivator 2, 0302 clinical medicine, Glucocorticoid receptor, Corticosterone, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, In Situ Hybridization, Mice, Knockout, 0303 health sciences, Adrenal gland, Adrenal cortex, Reverse Transcriptase Polymerase Chain Reaction, MESH: Transcription Factors, medicine.anatomical_structure, MESH: Pituitary-Adrenal System, Hypothalamus, Female, hormones, hormone substitutes, and hormone antagonists, Biotechnology, MESH: DNA Primers, endocrine system, medicine.medical_specialty, Hypothalamo-Hypophyseal System, 3-Hydroxysteroid Dehydrogenases, Biology, MESH: Hypothalamo-Hypophyseal System, MESH: Phosphoproteins, 03 medical and health sciences, MESH: In Situ Hybridization, Receptors, Glucocorticoid, Zona fasciculata, MESH: Mice, Inbred C57BL, Internal medicine, Genetics, medicine, Animals, MESH: 3-Hydroxysteroid Dehydrogenases, MESH: Mice, Molecular Biology, Adrenocortical Insufficiency, 030304 developmental biology, DNA Primers, Base Sequence, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Phosphoproteins, MESH: Male, Mice, Inbred C57BL, Steroid hormone, Endocrinology, chemistry, Adrenal Cortex, MESH: Adrenal Cortex, MESH: Corticosterone, MESH: Female, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; The transcription-intermediary-factor-2 (TIF-2) is a coactivator of the glucocorticoid receptor (GR), and its disruption would be expected to influence glucocorticoid-mediated control of the hypothalamo-pituitary-adrenal (HPA) axis. Here, we show that its targeted deletion in mice is associated with altered expression of several glucocorticoid-dependent components of HPA regulation (e.g., corticotropin-releasing hormone, vasopressin, ACTH, glucocorticoid receptors), suggestive of hyperactivity under basal conditions. At the same time, TIF-2(-/-) mice display significantly lower basal corticosterone levels and a sluggish and blunted initial secretory response to brief emotional and prolonged physical stress. Subsequent analysis revealed this discrepancy to result from pronounced aberrations in the structure and function of the adrenal gland, including the cytoarchitectural organization of the zona fasciculata and basal and stress-induced expression of key elements of steroid hormone synthesis, such as the steroidogenic acute regulatory (StAR) protein and 3beta-hydroxysteroid dehydrogenase (3beta-HSD). In addition, altered expression levels of two nuclear receptors, DAX-1 and steroidogenic factor 1 (SF-1), in the adrenal cortex strengthen the view that TIF-2 deletion disrupts adrenocortical development and steroid biosynthesis. Thus, hyperactivity of the hypothalamo-pituitary unit is ascribed to insidious adrenal insufficiency and impaired glucocorticoid feedback.

Published
2006

14. Cross-talk of vitamin D and glucocorticoids in hippocampal cells

Author

Beat Lutz, Hinrich Gronemeyer, Darja Obradovic, Theo Rein, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I

Subjects
MESH: Hippocampus, MESH: Receptors, Glucocorticoid, medicine.medical_treatment, MESH: Drug Interactions, MESH: Neurons, Hippocampal formation, Biochemistry, Hippocampus, MESH: Down-Regulation, chemistry.chemical_compound, 0302 clinical medicine, Glucocorticoid receptor, MESH: Vitamin D, Genes, Reporter, MESH: Animals, Drug Interactions, Phosphorylation, Vitamin D, Cells, Cultured, Mitogen-Activated Protein Kinase 1, Neurons, 0303 health sciences, Mitogen-Activated Protein Kinase 3, Cell Differentiation, MESH: Neuroprotective Agents, 3. Good health, Neuroprotective Agents, MESH: Mitogen-Activated Protein Kinase 3, Platelet-derived growth factor receptor, Glucocorticoid, hormones, hormone substitutes, and hormone antagonists, medicine.drug, MESH: Cells, Cultured, MESH: Mitogen-Activated Protein Kinase 1, Vitamin, MESH: Cell Differentiation, Transcriptional Activation, medicine.medical_specialty, Neurite, MESH: Rats, Down-Regulation, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Receptors, Glucocorticoid, Internal medicine, medicine, Vitamin D and neurology, Animals, Rats, Wistar, Glucocorticoids, 030304 developmental biology, MESH: Phosphorylation, Growth factor, MESH: Genes, Reporter, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Rats, Wistar, Rats, Endocrinology, chemistry, MESH: Trans-Activation (Genetics), biology.protein, MESH: Glucocorticoids, 030217 neurology & neurosurgery
Abstract

International audience; There is growing evidence for a role of vitamin D3 signalling in the brain. In this study, we investigated the influence of vitamin D3, in combination with glucocorticoids, on differentiation of the hippocampal progenitor line HIB5, as well as survival of rat primary hippocampal cells. In HIB5, pre-treatment with dexamethasone (Dex) alone inhibited neurite outgrowth and abolished activation of the mitogen-activated protein kinase (MAPK) pathway during platelet-derived growth factor (PDGF)-induced differentiation, consistent with previous findings. Interestingly, pre-treating HIB5 with vitamin D3 significantly reduced these effects of Dex and, in addition, lowered the transactivational function of the glucocorticoid receptor (GR) in transient reporter gene assays. A further impact of vitamin D3 on glucocorticoid effects was observed in a rat primary hippocampal culture known to be particularly sensitive to prolonged GR activation. In this model, Dex induced considerable cell death after 72 h of exposure in vitro. However, 24 h of pre-treatment with low doses of vitamin D3 substantially reduced the degree of Dex-induced apoptosis in primary hippocampal cells. Taken together, our experiments demonstrate a cross-talk between vitamin D3 and glucocorticoids in two hippocampal models, a feature that may have important implications in disorders with dysregulated glucocorticoid signalling, including major depression.

Published
2005

15. Effect of pyridoxine on the inhibition by dexamethasone of murine erythroleukemia cell differentiation

Author

Howard Beverley Osborne, Laboratoire de Biologie Moléculaire et Cellulaire (ER199), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Osborne, Howard Beverley

Subjects
MESH: Cell Differentiation, Receptors, Steroid, medicine.medical_specialty, MESH: Receptors, Glucocorticoid, MESH: Pyridoxine, medicine.medical_treatment, Cellular differentiation, MESH: Leukemia, Experimental, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Dexamethasone, Cell Line, Hemoglobins, Mice, Receptors, Glucocorticoid, Glucocorticoid receptor, Internal medicine, medicine, Extracellular, Animals, MESH: Animals, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, Molecular Biology, Leukemia, Experimental, MESH: Kinetics, Pyridoxine, Cell Differentiation, Cell Biology, MESH: Cell Line, Cell biology, Kinetics, Steroid hormone, MESH: Hemoglobins, Endocrinology, Cell culture, MESH: Dexamethasone, hormones, hormone substitutes, and hormone antagonists, Glucocorticoid, MESH: Receptors, Steroid, medicine.drug
Abstract

International audience; Glucocorticoids are known to inhibit the induced differentiation of murine erythroleukemia cells. I show here that the binding of glucocorticoid receptors to the intact nuclei of these cells is reduced by exogenous extracellular pyridoxine (1-4 mM). This reduction of glucocorticoid-receptor binding did not abrogate the inhibition by dexamethasone of the induced differentiation.

Published
1983

16. Comparison of dexamethasone binding and resistance to inhibition of induced differentiation in subclones of murine erythroleukemia cells

Author

H. Beverley Osborne, Osborne, Howard Beverley, Laboratoire de Biologie Moléculaire et Cellulaire (ER199), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Cell Differentiation, endocrine system, medicine.medical_specialty, MESH: Receptors, Glucocorticoid, MESH: Leukemia, Experimental, Drug Resistance, Biophysics, Chromosomal translocation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Diamines, Biology, Biochemistry, Dexamethasone, Hexamethylene bisacetamide, Mice, Receptors, Glucocorticoid, Internal medicine, Acetamides, polycyclic compounds, medicine, Animals, MESH: Animals, Erythroleukemia cell, MESH: Mice, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Leukemia, Experimental, MESH: Clone Cells, Cell Differentiation, MESH: Diamines, Cell Biology, MESH: Acetamides, Molecular biology, Clone Cells, Chromatin, Endocrinology, Hormone receptor, MESH: Dexamethasone, Time course, MESH: Drug Resistance, Leukemia, Erythroblastic, Acute, MESH: Leukemia, Erythroblastic, Acute, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Hormone
Abstract

Subclones of the murine erythroleukemia cell line DS 19 with different sensitivities towards inhibition by dexamethasone (DEX) of the hexamethylene bisacetamide induced differentiation have been obtained. Scatchard analysis of DEX binding to whole cells and the time course of DEX binding to nuclei show that resistance to inhibition of erythrodifferentiation by DEX is neither associated with a reduction in specific binding of the hormone nor in a lack of activation or translocation to the nuclei of hormone receptor complexes. Hence resistance in these subclones must result from a defect at an event after binding of hormone-receptor complexes to chromatin if inhibition of differentiation is mediated by these complexes.

Published
1981

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